My work has three main research projects with a long-term goal of identifying new drug targets for treating addiction/overdose. The first project is to dissect the role of the microbiome as a non-genetic regulator of phenotypic variation observed in the Diversity Outbred Mice. The second project is a response to the opioid epidemic, where we identify loci associated with opioid-induced respiratory depression through QTL mapping. We have identified loci, a locus-specific to the respiratory depressing effects of morphine, and two independent loci that are responsible for the survival time of mice in response to a lethal dose of both morphine and fentanyl. In addition to QTL mapping, I am using transcriptome profiling of respiratory control regions of the brainstem of Collaborative Cross strains to correlate transcript abundance with basal respiratory traits and opioid-specific phenotypes of the Collaborative Cross mice. The third project is focused on utilizing integrative functional genomics to identify addiction-related genes and pathways. This work is situated as the interface betweenin silico and in vivo studies, whereby data are mined and integrated, then tested using animal models. One approach that we have pioneered is to perform cross-species analysis by using GeneWeaver, a database and a suite of tools that utilize graph-based algorithms to identify convergent evidence from diverse datasets across numerous species to elucidate and validate genes' roles in disease.
